Evaluation of GJB 2 and GJB 6 Mutations in Patients Afflicted with Non-syndromic Hearing Loss (original) (raw)
Related papers
GJB2 and GJB6 genes mutations in children with non-syndromic hearing loss
Revista Romana de Medicina de Laborator, 2017
Introduction. At the moment there is not enough data in Romania about the incidence of the main genetic mutations which can cause hearing loss. Objective. The current research aims to determine on a representative sample the prevalence of two mutations of genes GJB2 -c.35delG and p.W24X- and two mutations of genes GJB6 -del(GJB6-D13S1830), del(GJB6-D13S1854) respectively - in patients with congenital nonsyndromic sensorineural hearing loss (CNSHL). Methods: The sample group included 179 children with CNSHL. The evaluation consist in: a.Clinical, laboratory and imagistic examination; b.ENT exam and audiological evaluation. c.Two methods (semi-nested PCR technique followed by RFLP, validated with ARMS-PCR analysis) for detection of c.35delG and pW24X mutations; d.PCR-multiplex technique for detecting del(GJB6-D13S1830) and del (GJB6-D13S1854). Results: The audiological diagnosis was: profound hearing loss in 116 patients (64.8%), severe hearing loss in 29 children (16.2%) and moderate...
PLOS ONE, 2021
Hearing impairment (HI) is a highly heterogeneous genetic disorder and is classified into nonsyndromic (without any other clinical manifestations) and syndromic (if combined with other clinical presentations) forms. Variations in GJB2 gene are the leading cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) in several populations worldwide. This study was carried out to investigate the prevalence of GJB2 variations in severe-to-profound hearing impaired families of Southern Punjab of Pakistan. Ten families segregating ARNSHL were recruited from different areas of the region. Sanger sequencing of GJB2 coding region was carried out. In two out of ten families, NM_004004:c.*71G>A (p.(Trp24*)) and NM_004004:c.358_360del (p.(Glu120del)) homozygous variants were identified as the cause of hearing loss. Our study showed that GJB2-related hearing loss accounts for at least 20% of all cases with severe-to-profound hearing loss in the Southern Punjab population of Pakistan.
Journal of Research in Medical Sciences
This high frequency of HL, at least in part, steams from high consanguineous marriage rate (38.6%) in Iranian population. [3] In the last decades, myriad investigations have been carried out to disclose etiopathogenesis of HL that revolutionized our knowledge concerning molecular basis of this disorder. However, owing to high genetic heterogeneity and multiple phenocopies of HL, more studies in this area are needed. Background: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2) and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL) in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. Results: We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. Conclusion: This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran.
Intractable & rare diseases research, 2021
Non-syndromic sensory neural hearing defect is one of the genetic diseases inherited from parents to offerings. The autosomal recessive form affects a large population worldwide and has become a major concern in the social and professional lives of many people. There are many factors and genes which are involved in hearing loss but the Gap Junction Beta 2 (GJB2) gene which encodes the connexin 26 protein, is a major cause of non-syndromic recessive deafness (NSRD). This study aims to record and analyze GJB2 gene mutations in the hearing-impaired population of North Karnataka, India. In this study, we included 368 congenitally hearing-impaired children from North Karnataka, India, under 18 years of age. After thorough clinical examinations, patient's history and proper audiological results, peripheral blood samples were collected and subjected to genetic analysis. We recorded that 54.8% of the NSRD cases have an autosomal recessive mutation in the coding region of the GJB2 gene. ...
2021
Introduction: Hearing loss (HL), with more than 100 gene loci, is the most common sensorineural defects in humans. The mutations in two GJB2 and GJB6 (Gap Junction Protein Beta 2, 6) genes are responsible for nearly 50% of autosomal recessive nonsyndromic hearing loss. The aim of the present study was to evaluate polymorphisms of 111C>T (rs7329857) and 337G>T (rs7333214) in GJB2 (encoding connexin 26) and GJB6 (encoding connexin 32) genes, respectively. Materials and Methods: In this study, 32 blood samples were obtained from Iranian patients with HL defect and 32 normal blood samples were prepared. After genomic deoxyribonucleic acid extraction, genotyping in rs7333214 and rs7329857 polymorphisms was conducted using tetra-amplification refractory mutation system-polymerase chain reaction and the obtained data were analyzed. Results: In this study, the prevalence rates of CC, CT, and TT genotypes in GJB2 gene were reported as 84.4%, 68.7%, and 0% in the affected subjects and 0...
Journal of critical reviews, 2020
Hearing impairment is a major disorder ranging from slight, moderate to profound. The genetic cause of the non syndromichearing impairment is exceptionally heterogeneous. Despite of this, a change in the connexin genes is a major contributor. Several mutations in the GJB2 gene and deletion in GJB6 are found to be related with hearing impairment. The analyses found that the average frequency of GJB2 mutation is varying among different regions. Materials and Methods: In this manuscript, we have reviewed 12 previous publications. In which around 2546 probands were included to analyse the prevalence and type of mutation in the GJB2 gene. Results: Our studyfound several mutations and the common mutations are c.71G>A, c.230G>A, c.235DelC, c.167delTA, and 35delG. The most common mutation in GJB2 is c.71G>A (p.W24X) followed by 35delG. The etiology of hearing impairment is of multi-factorial and K+-toxicity is the most accepted hypothesis to explain the cause of the hearing impairment. Conclusion: The mutations in the GJB2 gene are responsible for the contribution of up to around 36%. Regarding GJB2 mutation c.71G>A (p.W24X), a tryptophan stop codon is the most common mutation. Keywords: GJB2, connexin genes, hearing impairment, Indian population and sensory disorder INTRODUCTION Hearing impairment refers to the hearing loss range from slight to profound. It is the most common problem among sensory disorders, and leading a cause of disability worldwide (WHO). Hearing loss affects 5% of the world population and 60% of cases are due to preventable causes (WHO). Hearing Impairment occurs more in developing than developed countries and several genes are causing the hearing impairment. They can cause 70% non-syndromic isolated hearing impairment and 30% syndromic that can be associated with other medical abnormalities[1]. A study done in 1995 suggests that 60% of the cases with hearing impairment are well established with genetic etiology [2] , and among them 85% of these cases exhibiting autosomal recessive, dominant, X-linked or mitochondrial inheritance showing significant genetic heterogeneity. Hearing impairment is common among the sensory congenital disorders with the prevalence of 1-3 in 1000 live births in the general population, and 50-60% of these cases have genetic etiologies [3]. There is a group of proteins called connexins, play an important role in intracellular communication of ear [4]. These proteins are then coded by genes called gap junction genes and among them GJB2 and GJB6 are commonly associated with hearing impairment. The GJB2 and GJB6 genes codes for gap junction protein beta 2 gap junction protein beta 6. The GJB2 and GJB6 are the predominant isoform and co-expressed in an epithelial supporting cell of cochlea and function as a gap junction. It was found mutations in these genes are more frequent with hearing impairments [5]. GJB2 gene has a simple genomic structure with 680 base pairs [6] that has a role of homeostasis in cochlear fluids that is endolymph and perilymph by recycling of potassium ions in the inner ear [7]. The mutation in connexion 26 is primarily known for the causation of prelingual hearing impairment and it was the first reported by Kelsell et al in 1997 causing autosomal recessive non-syndromic deafness [8]. Mutations in the GJB2 and GJB6 genes are mostly found to be autosomal-recessive nonsyndromic hearing loss in many populations. The mutation includes frame shift or deletion resulting in a short non-functional truncated form of the protein [9]. Mutations in these genes account for up to 50% of all cases of the prelingual deafness in many tested
GJB2 mutations in Iranians with autosomal recessive non-syndromic sensorineural hearing loss
Human Mutation, 2002
Hereditary hearing loss (HHL) is an extremely common disorder. About 70% of HHL is non-syndromic, with autosomal recessive forms accounting for ∼85% of the genetic load. Although very heterogeneous, the most common cause of HHL in many different world populations is mutations of GJB2, a gene that encodes the gap junction protein connexin 26 (Cx26). This study investigates the contribution of GJB2 to the autosomal recessive non-syndromic deafness (ARNSD) load in the Iranian population. One hundred sixty eight persons from 83 families were studied. GJB2-related deafness was diagnosed in 9 families (4, 35delG homozygotes; 3, 35delG compound heterozygotes; 1, W24X homozygote; 1, non-35delG compound heterozygote). The carrier frequency of the 35delG allele in this population was ∼1% (1/83). Because the relative frequency of Cx26 mutations is much less than in the other populations, it is possible that mutations in other genes play a major role in ARNSD in Iran. © 2002Wiley-Liss, Inc
Journal of Audiology and Otology, 2018
Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARN-SHL cases in the Kurdish population. Subjects and Methods: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). Results: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.